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Study to overcome metastasis and targeted drug-resistance of lung cancer

Research Project

Project/Area Number 24390209
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKanazawa University

Principal Investigator

YANO Seiji  金沢大学, がん進展制御研究所, 教授 (30294672)

Co-Investigator(Kenkyū-buntansha) EBI Hiromichi  金沢大学, がん進展制御研究所, 助教 (00645145)
OHTSUBO Koshiro  金沢大学, 大学病院, 講師 (60361987)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords分子標的薬耐性 / 脳転移 / 骨転移 / がん性胸膜炎 / 転移 / イメージング / がん性胸水 / がん性髄膜炎 / 肺がん / ALK阻害薬耐性 / BIM遺伝子多型 / EGFR阻害薬耐性 / mTOR阻害薬 / 個別化医療 / ボリノスタット
Outline of Final Research Achievements

To elucidate mechanism of targeted drug resistance in metastatic lesions, we established in vivo imaging models for pleural carcinomatosis and bone/brain metastases, which are resistant to targeted drugs, of EGFR mutant or ALK fusion positive lung cancer cell lines. We found that resistant tumors consist of a heterogeneous mixture of functionally distinct cancer cells with different resistant mechanisms. Moreover, our observation indicated that we should be careful for toxicity of combined therapy which overcome targeted drug resistance caused by multiple mechanisms.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report

Research Products

(54 results)

All 2015 2014 2013 2012 Other

All Journal Article (33 results) (of which Peer Reviewed: 33 results,  Open Access: 5 results,  Acknowledgement Compliant: 11 results) Presentation (17 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Lack of association between the BIM deletion polymorphism and the risk of lung cancer with and without EGFR mutations.2015

    • Author(s)
      Ebi H, Yano S, et al.
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 10 Pages: 59-66

    • DOI

      10.1097/jto.0000000000000371

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Therapeutic activity of glycoengineered anti-GM2 antibody against malignant pleural mesothelioma.2015

    • Author(s)
      Li Q, Yano S, et al.
    • Journal Title

      Cancer Sci

      Volume: 106 Pages: 102-107

    • DOI

      10.1111/cas.12575

    • NAID

      120005666336

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.2015

    • Author(s)
      Nanjo S, Yano S, et al.
    • Journal Title

      Cancer Sci.

      Volume: 106 Pages: 244-252

    • DOI

      10.1111/cas.12600

    • NAID

      120005830611

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] LPP inhibits collective cell migration during lung cancer dissemination.2015

    • Author(s)
      Tanaka M, Yano S, et al.
    • Journal Title

      Oncogene

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TAS-115, a novel inhibitor of VEGFR-2 and Met, combined with erlotinib prevented re-growth of HGF-triggered erlotinib resistant lung cancer harboring EGFR mutation.2014

    • Author(s)
      Nakade J, Yano S, et al.
    • Journal Title

      Journal of Thoracic Oncology

      Volume: 9 Pages: 775-783

    • DOI

      10.1097/jto.0000000000000170

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.2014

    • Author(s)
      Tanimoto A, Yano S, et al.
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 4920-8

    • NAID

      120005830567

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer.2014

    • Author(s)
      Ohtsubo K, Yano S, et al.
    • Journal Title

      Pancreas

      Volume: 43 Pages: 1093-100

    • DOI

      10.1097/mpa.0000000000000168

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Distinct allelic expression patterns of imprinted IGF2 in adenocarcinoma and squamous cell carcinoma of the lung.2014

    • Author(s)
      Ozaki S, Yano S, et al.
    • Journal Title

      Oncol Lett

      Volume: 8 Pages: 2561-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The current state of molecularly targeted drugs targeting HGF/Met.2014

    • Author(s)
      Yano S, Nakagawa T.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 44 Pages: 9-12

    • DOI

      10.1093/jjco/hyt188

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Not just gRASping at flaws: finding vulnerabilities to develop novel therapies for treating KRAS mutant cancers.2014

    • Author(s)
      Ebi H, Yano S, et al.
    • Journal Title

      Cancer Science

      Volume: 105 Pages: 499505-499505

    • DOI

      10.1111/cas.12383

    • NAID

      120005830600

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical significance of epidermal growth factor receptor tyrosine kinase inhibitors: Sensitivity and resistance.2014

    • Author(s)
      Takeuchi S, Yano S.
    • Journal Title

      Respir Investig

      Volume: 52 Pages: 348-56

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Surfactant protein a suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages.2014

    • Author(s)
      Mitsuhashi A, Yano S, et al.
    • Journal Title

      The American Journal of Pathology

      Volume: 182 Pages: 1843-1853

    • DOI

      10.1016/j.ajpath.2013.01.030

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect and antiangiogenic potential of the mTOR inhibitor temsirolimus against malignant pleural mesothelioma.2014

    • Author(s)
      Moriya M, Yano S, et al.
    • Journal Title

      Oncol Rep

      Volume: 31 Pages: 1109-15

    • DOI

      10.3892/or.2013.2948

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ability of the Met kinase inhibitor crizotinib and new generation EGFR inhibitors to overcome resistance to EGFR inhibitors.2013

    • Author(s)
      Nanjo S, Yano S, et al.
    • Journal Title

      PLoS ONE

      Volume: 8

    • DOI

      10.1371/journal.pone.0084700

    • NAID

      120005368227

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paracrine activation of MET promotes peritoneal carcinomatosis in scirrhous gastric cancer.2013

    • Author(s)
      Zhao L, Yano S, et al.
    • Journal Title

      Cancer Science

      Volume: 104 Pages: 1640-1646

    • DOI

      10.1111/cas.12301

    • NAID

      120005830610

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition.2013

    • Author(s)
      Nakagawa T, Yano S, et al.
    • Journal Title

      Cancer Res

      Volume: 73 Pages: 2428-2434

    • DOI

      10.1158/0008-5472.can-12-3479

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The novel phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor, BEZ235, circumvents erlotinib resistance of epidermal growth factor receptor mutant lung cancer cells triggered by hepatocyte growth factor.2013

    • Author(s)
      Sano T, Yano S, et al.
    • Journal Title

      IntJ Cancer

      Volume: 133 Pages: 505-13

    • DOI

      10.1002/ijc.28034

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTOR inhibitors control erlotinib-resistance of EGFR mutant lung cancer cells triggered by HGF.2013

    • Author(s)
      Ishikawa D, Yano S, et al.
    • Journal Title

      Plos One

      Volume: 8

    • DOI

      10.1371/journal.pone.0062104

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR activating and gatekeeper mutations.2013

    • Author(s)
      Yamada T, Yano S, et al.
    • Journal Title

      Oncogene

      Volume: 32 Pages: 4427-35

    • DOI

      10.1038/onc.2012.446

    • NAID

      120004997024

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synchronous triple cancers of the pancreas, stomach, and cecum treated with S-1 followed by pancrelipase treatment of pancreatic exocrine insufficiency.2013

    • Author(s)
      Ohtsubo K, Yano S, et al.
    • Journal Title

      JOP

      Volume: 14 Pages: 515-20

    • DOI

      10.6092/1590-8577/1719

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KDM5B histone demethylase controls epithelial-mesenchymal transition of cancer cells by regulating the expression of the microRNA-200 family.2013

    • Author(s)
      Enkhbaatar Z, Yano S, et al.
    • Journal Title

      Cell Cycle

      Volume: 12 Pages: 2100-12

    • DOI

      10.4161/cc.25142

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1.2013

    • Author(s)
      Ebi H, Yano S, et al.
    • Journal Title

      PNAS

      Volume: 110 Pages: 21124-9

    • DOI

      10.1073/pnas.1314124110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EGFR-TKI resistance due to BIM polymorphism can be circumvented by incombination with HDAC inhibition.2013

    • Author(s)
      Nakagawa T, Yano S, et al.
    • Journal Title

      Cancer Res

      Volume: 73(8) Pages: 2428-34

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] E7050, a Met kinase inhibitor, reverses three different mechanisms of hepatocyte growth factor-induced resistance to tyrosine kinase inhibitors in EGFR mutant lung cancer cells2012

    • Author(s)
      Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Uenaka T, Yano S
    • Journal Title

      Clin Cancer Res.

      Volume: 18 Pages: 1663-1671

    • DOI

      10.1158/1078-0432.ccr-11-1171

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor-resistance in EML4-ALK lung cancer cells.2012

    • Author(s)
      Yamada T, Yano S, et al.
    • Journal Title

      Clin Cancer Res

      Volume: 18(13) Pages: 3592-602

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual inhibition of Met kinase and angiogenesis to overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer.2012

    • Author(s)
      Takeuchi S, Yano S, et al.
    • Journal Title

      Am J Pathol

      Volume: 181(3) Pages: 1034-43

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endoscopic findings of upper gastrointestinal lesions in patients withpancreatic cancer.2012

    • Author(s)
      Ohtsubo K, Yano S, et al.
    • Journal Title

      JOP

      Volume: 13(4) Pages: 420-6

    • DOI

      10.6092/1590-8577/749

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combined therapy with mutant-selective EGFR inhibitor and Met kinase inhibitor for overcoming erlotinib resistance in EGFR mutant lung cancer.2012

    • Author(s)
      Nakagawa T,Yano S, et al.
    • Journal Title

      Mol Cancer Ther

      Volume: 11(10) Pages: 2149-57

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hsp90 Inhibition Overcomes HGF Triggering Resistance to EGFR-TKIs in EGFR-Mutant Lung Cancer by Decreasing Client Protein Expression and Angiogenesis2012

    • Author(s)
      Koizumi H, Yamada T, Takeuchi S, Nakagawa T, Kita K, Nakamura T, Matsumoto K, Suda K, Mitsudomi T, and Yano S
    • Journal Title

      J Thoracic Oncol

      Volume: Vol. 7: no.7 Pages: 1078-1085

    • DOI

      10.1097/jto.0b013e3182519a2c

    • NAID

      40019570662

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte growth factor induces resistance to anti-epidermal growth factor receptor antibody in lung cancer2012

    • Author(s)
      Yamada T, Takeuchi S, Kita K, Bando H, Nakamura T, Matsumoto K, Yano S
    • Journal Title

      J Thoracic Oncol

      Volume: 7 Pages: 272-280

    • DOI

      10.1097/jto.0b013e3182398e69

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of acquired resistance-related molecules in Japanese patients with NSCLC treated with an EGFR-TKI.2012

    • Author(s)
      Uramoto H, Yano S, et al.
    • Journal Title

      Anticancer Res

      Volume: 32(9) Pages: 3785-90

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma2012

    • Author(s)
      Kurai J, Chikumi HT, Hamada H, Yano S, , Hashimoto K, Takata M, Sako T, Yamaguchi K, Kinoshita N, Watanabe M, Touge H, Makino H, Igishi Shimizu E
    • Journal Title

      Int J Oncol

      Volume: 41 Pages: 1610-1618

    • DOI

      10.3892/ijo.2012.1607

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T790M is associated with a favorable prognosis in Japanese patients treated with an EGFR-TKI2012

    • Author(s)
      Uramoto T, Yano S, Tanaka F
    • Journal Title

      Lung Cancer

      Volume: 76 Pages: 129-130

    • DOI

      10.1016/j.lungcan.2012.01.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Therapeutic activity of glycoengineered anti-GM2 antibody BIW-8962 against malignant pleural mesothelioma.2015

    • Author(s)
      Yano S.
    • Organizer
      15th Annual Targeted Therapies of The Treatment of Lung Cancer
    • Place of Presentation
      Hotel Fairmont Miramar Wilshire Boulevard (USA)
    • Year and Date
      2015-02-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Bone microenvironment conferes Hsp90 inhibitor resistance in the metastatic small sell lung cancer.2015

    • Author(s)
      Yano S.
    • Organizer
      Joint International Symposium on TGF-βFamily and Cancer
    • Place of Presentation
      International Congress Center EPOCHAL TSUKUBA (Japan)
    • Year and Date
      2015-01-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Resistance to EGFR-TKI in EGFR mutant lung cancer.2014

    • Author(s)
      矢野聖二
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳転移:腫瘍内科の視点から.2014

    • Author(s)
      矢野聖二
    • Organizer
      第52回日本癌治療学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺がんの骨転移のメカニズムと分子標的治療.2014

    • Author(s)
      矢野聖二
    • Organizer
      第23回日本がん転移学会学術集会・総会
    • Place of Presentation
      金沢市文化ホール
    • Year and Date
      2014-07-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肺がんの分子標的治療薬耐性の機構解明と耐性克服治療開発.2014

    • Author(s)
      矢野聖二
    • Organizer
      第18回日本がん分子標的治療学会学術集会
    • Place of Presentation
      ホテルメトロポリタン仙台
    • Year and Date
      2014-06-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 日本における腫瘍内科教育の今後~分子標的薬体制の克服絵を目指した研究を通して~2014

    • Author(s)
      矢野聖二
    • Organizer
      第111回日本内科学会講演会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2014-04-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Strategy to Treat EGFR-TKI Resistance in EGFR Mutant Lung Cancer.2012

    • Author(s)
      Yano S.
    • Organizer
      5th Asia Pacific Lung Cancer Conference.(APLCC)
    • Place of Presentation
      Hilton Fukuoka Sea Hawk
    • Year and Date
      2012-11-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] Ligand-stimulated receptor activation as novel targets to overcome resistance to molecular targeted drugs in lung cancer.2012

    • Author(s)
      矢野聖二
    • Organizer
      第71回日本癌学会学術集会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular mechanisms of EGFR- TKI resistance and strategy with HGF-Met inhibitors to overcome the resistance.2012

    • Author(s)
      矢野聖二
    • Organizer
      第10回日本臨床腫瘍学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-07-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor-resistance in EML4-ALK lung cancer cells.2012

    • Author(s)
      Yano S.
    • Organizer
      AACR Molecularly Targeted Therapies: Mechanisms of Resistance Conference
    • Place of Presentation
      The Westin San Diego
    • Year and Date
      2012-05-09
    • Related Report
      2012 Annual Research Report
  • [Presentation] 分子標的薬剤の耐性機序及びその耐性克服を目指した臨床戦略.

    • Author(s)
      矢野聖二
    • Organizer
      第22回日本がん転移学会学術集会・総会
    • Place of Presentation
      ホテル ブエナビスタ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mechanisms of EGFR-TKI resistance and therapeutic strategies.

    • Author(s)
      矢野聖二
    • Organizer
      第11回日本臨床腫瘍学会学術集会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Annual Research Report
  • [Presentation] Circumvention of molecular targeted drug-resistance in lung cancer.

    • Author(s)
      矢野聖二
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mechanisms of EGFR-TKI resistance and therapeutic strategies in lung cancer.

    • Author(s)
      矢野聖二
    • Organizer
      第54回日本肺癌学会総会
    • Place of Presentation
      ホテルニューオータニ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Novel acquired resistance of molecular-targeted therapy for lung cancer.

    • Author(s)
      Yano S.
    • Organizer
      American Thoracic Society 2013. (Meet the Professor)
    • Place of Presentation
      Pennsylvania Convention Center, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Resistance to EGFR TKIs.

    • Author(s)
      Yano S.
    • Organizer
      IASLC 15th World Conference on Lung Cancer
    • Place of Presentation
      Sydney Exhibition & Convention Centre, Australia
    • Related Report
      2013 Annual Research Report
  • [Remarks] 金沢大学附属病院がん高度先進治療センター 金沢大学がん進展制御研究所/腫瘍内科

    • URL

      http://syuyounaika.w3.kanazawa-u.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 金沢大学附属病院 がん高度先進治療センター 金沢大学がん進展制御研究所/腫瘍内科

    • URL

      http://syuyounaika.w3.kanazawa-u.ac.jp/

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://syuyounaika.w3.kanazawa-u.ac.jp

    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 肺癌患者の治療の有効性の予測検査方法及び肺癌治療剤のスクリーニング方法2013

    • Inventor(s)
      矢野聖二、竹内伸司、中川学之
    • Industrial Property Rights Holder
      矢野聖二、竹内伸司、中川学之
    • Filing Date
      2013-03-04
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-23   Modified: 2023-03-16  

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